Effects of arsenic and its metabolites on p53 gene expression in BEAS-2B cells / 环境与职业医学

Background Arsenic is a human carcinogen. Arsenic and its metabolites affect the expression of p53, but whether there are any changes of p53 phosphorylation and ubiquitination levels in human bronchial epithelium cells (BEAS-2B) are not clear after exposure to arsenic and its metabolites. Objective To study the effects of arsenic and its metabolites monomethylarsic acid (MMA) and dimethylarsinic acid (DMA) on the expression of tumor suppressor gene p53 in BEAS-2B cells. Methods Different concentrations of sodium arsenite (NaAsO2) were used to infect BEAS-2B cells, and the cell viability was detected with CCK-8 reagent to determine the dose and time of NaAsO2 used for the following study. Based on the results of cell viability, the cells were divided into two panels: a sodium arsenide panel and an arsenic methylation metabolite penal. The doses of sodium arsenite were 0, 2, 4, and 6 μmol·L−1 NaAsO2; the arsenic methylation metabolite panel consisted of 0 μmol·L−1 NaAsO2 group (control), 6 μmol· L−1 MMA group, 6 μmol· L−1 DMA group， and 6 μmol· L−1 NaAsO2 group. The cells were collected after 48 h treatment, and the total protein and total RNA were extracted. The relative levels of p53 mRNA expression were determined by quantitative real-time polymerase chain reaction (qRT-PCR), the relative expression levels of p53 protein, p53 Ser9 and Ser15 phosphorylated proteins were determined by Western blot, and the level of p53 ubiquitination was detected by co-immunoprecipitation (CO-IP). Results Compared with the control group, the cell viability rates in all BEAS-2B cells treated by NaAsO2 were significantly reduced (P<0.05), and the 50% cell viability was observed at 6 μmol·L−1. Compared with the control group, the relative expression level of p53 mRNA gradually decreased after NaAsO2 (2, 4, 6 μmol·L−1) treatment (P<0.05), the relative expression levels of p53 protein and Ser9 phosphorylated protein induced by NaAsO2 also decreased gradually (P<0.05), and the relative expression level of p53 Ser15 phosphorylated protein induced by NaAsO2 followed the same pattern, but it was only lower than that of the control group in the 6 μmol·L−1 NaAsO2 group (P<0.05). Compared with the control group, there were no significant effects on the relative expression levels of p53 mRNA, p53 protein, Ser9 and Ser15 phosphorylated proteins in the MMA group and the DMA group. Compared with the control group, the expression level of p53 ubiquitination was significantly decreased and the expression of K48 ubiquitination decreased significantly after NaAsO2 infection. Conclusion Arsenic causes a decrease in the expression of the p53 protein in BEAS-2B cells, largely due to inhibition of the phosphorylated pathway and a decrease in mRNA expression, and protein changes caused by a decrease in p53 ubiquitination do not play a dominant role. MMA and DMA do not affect p53 gene expression.

Myocardial contrast echocardiography combined with speckle tracking imaging for evaluating protective effect of 2-aminoethoxydiphenyl borate on heart of arsenic poisoned rats / 中国医学影像技术

Objective To observe the value of myocardial contrast echocardiography(MCE)combined with speckle tracking imaging(STI)for evaluating the protective effect of 2-aminoethoxydiphenyl borate(2-APB)on heart of arsenic poisoned rats.Methods Forty rats were randomly divided into low-and high-dose 2-APB intervention after arsenic trioxide(ATO)poisoned group(2-APBL group and 2-APBH group),simple ATO poisoned group(ATO group),simple 2-APB intervention group(2-APB group)and control group(each n=8).5 mg/kg ATO were intraperitoneally injected in 2-APBL group,2-APBH group and ATO group,while equal dose physiological saline were injected in 2-APB group and control group,respectively.Then 2,4 and 4 mg/kg 2-APB were intraperitoneally injected in 2-APBL group,2-APBH group and 2-APB group,while equal doses physiological saline were injected in ATO group and control group,respectively.MCE and STI were performed,serum myocardial injury markers were tested,sarcoplasmic reticulum Ca2+-ATPase(SERCA)was examinated,and finally myocardial pathological examination was performed.The above indexes were compared among groups and between each 2 groups,and correlation analysis was performed.Results Significant differences of left ventricular fractional shortening(LVFS),left ventricular ejection fraction(LVEF),wash in slope(WIS),peak intensity(PI),WIS×PI,area under the curve(AUC),global circumferential strain(GCS)in each layer of myocardium,as well as glutamic-oxaloacetic transaminase(GOT),creatine kinase(CK),lactate dehydrogenase(LDH)and SERCA were found among 5 groups(all P＜0.05).The above indexes substantially increased or decreased sequentially ATO group,2-APBL group,2-APBH group and 2-APB group/control group(all P＜0.05).WIS,PI,WIS × PI and GCS of rat endo-myocardium,GSC of mid-myocardium and GCS of epi-myocardium all positively correlated with SERCA(r=0.874,0.893,0.920,0.916,0.848,0.783,all P＜0.05).Conclusion MCE combined with STI,especially WISXPI and GCS of endo-myocardium could be used to evaluate the protective effect of 2-APB on heart of arsenic poisoned rats.

Correlation Between Expression of HIF-1α and Prognosis of Arsenic-containing Chinese Herbal Compound in Treatment of Myelodysplastic Syndrome / 中国实验方剂学杂志

ObjectiveMyelodysplastic syndromes （MDS） is a group of clonal hematopoietic stem cell disorders，and this study aims to investigate the expression of hypoxia-inducible factor-1α（HIF-1α） in the bone marrow cells of patients with MDS and its correlation with the clinical features of MDS，the therapeutic efficacy of arsenic-containing Chineseherbal compound，and the survival prognosis. MethodAccording to the inclusion and exclusion criteria，27 MDS patients treated with arsenic-containing Chinese herbal compound in the Department of Hematology，Xiyuan Hospital，China Academy of Chinese Medical Sciences from January 2022 to September 2022 were included，and their bone marrow samples were collected by myelotomy. HIF-1α expression level in bone marrow cells was detected by real-time polymerase chain reaction （PCR） to analyze its correlation with clinical features，and logistic and Cox regression was used to analyze the risk factors affecting the efficacy and prognostic survival of MDS patients. ResultThe HIF-1α mRNA expression level was lower in bone marrow cells of MDS patients than in healthy subjects. HIF-1α was positively correlated with the degree of myelodysplasia（r=0.384，P<0.05） and bone marrow granulocytic system%（G%）（r=0.560，P<0.01）. Logistic regression showed that HIF-1α was a risk factor for the prognosis in the follow-up of the efficacy of treatment（P<0.05）and Cox regression showed that HIF-1α was an independent factor affecting the survival prognosis of MDS patients ［odds ratio（OR）=398.968，95% confidence interval（CI）（1.281，116 858.743），P<0.05］. ConclusionThe level of HIF-1α expression in bone marrow cells of MDS patients was closely related to the degree of clinical myelodysplasia and G%，and HIF-1α was a risk factor for the efficacy for and survival prognosis of MDS patients.

Research progress on roles and mechanisms of DNA hydroxymethylation in health effects induced by arsenic exposure / 环境与职业医学

Arsenic, a naturally occurring metal-like chemical element, is one of the 10 chemicals of major public concerns listed by the World Health Organization as harmful to the environment and human health. It can enter the human body through breathing, intaking food, drinking water, skin exposure, and other ways, and long-term exposure to arsenic can cause cancer of multiple organs and impaired function of multiple systems. Epigenetic mechanisms play an important role in arsenic-induced health effects, and research suggested that the carcinogenicity of arsenic may be associated with epigenetic changes. Previous studies focused on the effects of arsenic on DNA methylation modification. In recent years, research showed that 5-hydroxymethylcytosine (5-hmC), an intermediate of active demethylation of DNA, can act as a sensitive epigenetic mark and play a crucial role as a "bridge" between arsenic exposure and health effects. Based on the latest research progress on the role of DNA hydroxymethylation in the health effects associated with arsenic exposure, this article briefly described the relationship between the health effects of arsenic exposure and DNA hydroxymethylation, summarized the possible mechanisms of DNA hydroxymethylation in the health effects associated with arsenic exposure, and provided a scientific basis for preventing and treating the health effects associated with arsenic exposure.

Study on the mechanism of astragalus glycyrrhiza decoction regulating SIRT1 / FOXO1 pathway to prevent QT interval prolongation induced by arsenic trioxide based on metabolomics / 中国临床药理学与治疗学

AIM: To explore the protective effect of astragalus glycyrrhiza decoction (AGD) on arsenic trioxide (ATO)-induced QT interval prolongation and its mechanism based on metabonomics. METHODS: The model of ATO-induced QT interval prolongation in rats was established, and ECG, blood routine, and metabonomics were detected, and the key targets were collected combined with network pharmacology. The possible candidate genes and pathways for the protective effect of AGD were screened by GO and KEGG enrichment analysis and then verified by experiments in vitro. RESULTS: AGD could significantly alleviate the ATO-induced QT interval of SD rats. GO enrichment analysis was mainly related to inflammatory response, reactive oxygen species, oxidative stress, inner cell vesicles, folds, inner cell vesicles, SMAD binding, R-SMAD binding, and signal receptor activator activity. KEGG analysis showed that it was mainly concentrated in the PI3K-Akt signal pathway, lipid and arteriosclerosis, FOXO signal pathway, TNF signal pathway, HIF-1, and other signal pathways. Through the H9c2 cell model in vitro, it was verified that AGD could reverse the expression of SIRT1 and FOXO1 proteins. CONCLUSION: AGD may improve the ATO-induced QT interval prolongation and reduce the cardiotoxicity of ATO by regulating the SIRT1 / FOXO1 signal pathway.

Two directions that cannot be ignored in the study of endemic fluorosis and endemic arsenicosis in China: long-term exposure to low-dose fluoride and arsenic, and non-target organ damage / 中华地方病学杂志

With the comprehensive implementation of prevention and control measures for endemic fluorosis and endemic arsenicosis in China, and in accordance with the World Health Organization (WHO) recommended drinking water standards and the Chinese standards of allowable daily fluoride intake and limit values of arsenic content in drinking water, Chinese residents have entered the era of low-dose fluoride and arsenic exposure. However, there have been few studies focused on the long-term health effects of exposure to low-dose fluoride and arsenic both domestically and internationally. Further more, study on non-target organs of fluoride and arsenic has been neglected. The conclusions are also inconsistent, and there is an urgent need for systematic study to clarify them. Accordingly, this paper proposes to establish a cohort of people exposed to low-dose fluoride and arsenic, systematically carry out study on the long-term health effects and mechanisms of low-dose fluoride and arsenic exposure, and promote China's prevention and control experience to the "the Belt and Road" countries, in order to provide a scientific basis for the formulation of prevention and control strategies and measures for endemic fluorosis and endemic arsenicosis under the new situation in China.

Research progress on the mechanism of PGC-1α, a key regulator of mitochondrial biogenesis, in arsenic-induced nervous system damage / 中华地方病学杂志

Arsenic, as a toxic substance that can affect human health, can cause various neurological disorders, including cognitive impairment, when excessive. Relevant epidemiological surveys and animal experimental studies have shown that exposure to arsenic can not only cause intellectual impairment and peripheral neuropathy in humans, but also lead to abnormal behavior in humans and animals. However, so far, the mechanism of arsenic induced damage to the nervous system is still unclear. Peroxisome proliferator activated receptor γ auxiliary activation factor 1α (PGC-1α), as a nuclear transcription coactivator, can interact with transcription factors or other coactivators and plays a role in biological processes such as mitochondrial biogenesis and energy metabolism. PGC-1α, by activating mitochondrial biogenesis, affecting energy metabolism, activating oxidative stress regulatory factors [catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), etc.], mitigates the damage to the central nervous system (CNS), peripheral nervous system (PNS), and blood-brain barrier (BBB) caused by arsenic. This article summarize the research progress of arsenic-induced neurological injury and the mechanism of PGC-1α's role in arsenic-induced neurological injury to provide a theoretical basis for further prevention and treatment of neurological diseases caused by arsenic.

Influencing factors of arsenic metabolism pattern of population in drinking-water-borne endemic arsenic poisoning areas / 中华地方病学杂志

Objective:To investigate the arsenic metabolism pattern and possible influencing factors in the population in drinking-water-borne endemic arsenic poisoning (drinking-water-borne arsenic poisoning for short) areas.Methods:In December 2004, a cluster sampling method was used to select arsenic poisoning population (arsenic poisoning group) and healthy population (control group) in drinking-water-borne arsenic poisoning area of Bayannur City, Inner Mongolia Autonomous Region as the survey subjects. A questionnaire survey was conducted. Arsenic content in drinking water at home of survey subjects, the levels of urinary arsenic and its metabolites, including [trivalent arsenic (As Ⅲ), inorganic arsenic (iAs), monomethylarsenic acid (pentavalent, MMA V), dimethylarsenic acid (pentavalent, DMA V), total arsenic (tAs), percentage of inorganic arsenic (iAs%), percentage of monomethylarsenic acid (MMA%), percentage of dimethylarsenic acid (DMA%), primary methylation index (PMI), secondary methylation index (SMI)] were tested using high performance liquid chromatography-inductively coupled plasma mass spectrometry; nail arsenic and nail selenium levels were tested using atomic fluorescence spectrometer. The influencing factors of arsenic metabolism pattern were analyzed by multiple linear regression. Results:A total of 536 survey subjects were included, including 155 individuals in the arsenic poisoning group and 381 in the control group. The water arsenic level ranged from 0.0 to 825.7 μg/L. Compared with the control group, there was no significant difference in the distribution of gender, education level and dental fluorosis in the arsenic poisoning group ( P > 0.05), but there were significant differences in the distribution of age, marital status, smoking, drinking and water arsenic ( P < 0.05). Compared with the control group, the levels of urinary As Ⅲ, iAs, MMA V, DMA V, tAs, MMA%, MMA/DMA and nail arsenic in the arsenic poisoning group were higher ( P < 0.05), while the levels of urinary DMA%, SMI and nail selenium were lower ( P < 0.05); but there was no statistically significant difference in the levels of urinary iAs% and PMI ( P > 0.05). Gender, education level, depth of wells, water arsenic, total number of wells and nail arsenic were the influencing factors of urinary As Ⅲ (β = - 19.82, - 23.83, 0.61, 0.21, 7.26, 2.98, P < 0.05). Age, depth of wells, water arsenic and nail arsenic were the influencing factors of urinary tAs (β = 3.18, 3.25, 1.31, 15.59, P < 0.05). Gender, education level, depth of wells, water arsenic, total number of wells and nail arsenic were the influencing factors of urinary iAs (β = - 20.47, - 25.90, 0.64, 0.25, 7.87, 3.11, P < 0.05). Age, gender, education level, water arsenic and nail arsenic were the influencing factors of urinary MMA V (β = 0.52, - 17.07, - 21.84, 0.22, 2.77, P < 0.05). Age, depth of wells, water arsenic and nail arsenic were the influencing factors of urinary DMA V (β = 2.35, 2.47, 0.85, 9.22, P < 0.05). Conclusions:Compared with healthy individuals, there are differences in arsenic metabolism pattern among individuals with drinking-water-borne arsenic poisoning. Age, gender, education level, depth of wells, water arsenic, total number of wells and nail arsenic may be influencing factors of different arsenic metabolism patterns.

Main causes of death of residents in arsenic poisoning areas in Inner Mongolia Autonomous Region from 2016 to 2021 / 中华地方病学杂志

Objective:To analyze the main causes of death of residents in arsenic poisoning areas of Inner Mongolia Autonomous Region, providing a scientific basis for preventing and controlling the long-term effects of arsenic poisoning and ensuring the health of residents.Methods:The data on the causes of death among residents in arsenic poisoning areas of Inner Mongolia Autonomous Region from 2016 to 2021 were collected from the population death information registration management system and the population information system of various league and city statistical bureaus in Inner Mongolia Autonomous Region. Residents were divided into exposed and non exposed groups based on whether they drank high arsenic water. SPSS 25.0 software was used to statistically analyze the crude mortality rate (CDR), standardized mortality rate (SMR), disease-specific mortality rate, proportion of causes of death, and order of causes of death.Results:Over the past 6 years, there was a total of 9 583 deaths, with an average annual CDR of 633.12/100 000 and an average annual SMR of 446.65/100 000. The CDR of each year showed a decreasing trend over time (χ 2 = 1 058.86, P < 0.001). Male CDR was higher than female CDR (χ 2 = 325.04, P < 0.001). Heart diseases and malignant tumors were the main causes of death for residents in arsenic poisoning areas, with proportions of 25.00% (2 396/9 583) and 18.86% (1 807/9 583), respectively. The top three leading causes of malignant tumor death were lung cancer, liver cancer and gastric cancer. Among residents who died from various diseases and malignant tumors, the SMR of the exposed group was higher than that of the non exposed group (χ 2 = 147.08, 26.26, P < 0.001). Conclusions:The main causes of death of residents in arsenic poisoning areas in Inner Mongolia Autonomous Region are heart diseases and malignant tumors, with lung cancer, liver cancer, and gastric cancer being the top three leading causes of death for malignant tumors. Although the arsenic poisoning areas in the entire region have basically achieved water improvement, the long-term effects of chronic arsenic exposure still exist.

Relationship between maternal arsenic exposure during pregnancy and congenital heart disease in offspring: A meta-analysis / 中华地方病学杂志

Objective:To systematically evaluate the correlation between maternal arsenic exposure during pregnancy and congenital heart disease (CHD) in offspring.Methods:Literature search was performed through databases such as PubMed, Web of Science, Embase, China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, and VIP.com to include epidemiological literature on association between maternal arsenic exposure during pregnancy and offspring CHD published domestically and internationally. The search was conducted from database establishment until November 2, 2022. Stata MP15 software was used for meta-analysis of binary variables, and I 2 statistics and Q test were used for heterogeneity test, fixed effect model or random effect model was selected based on the test results. Using OR value (95% CI) as the effect evaluation indicator, subgroup analysis was conducted based on CHD subtypes [conotruncal defects (CTD), atrioventricular septal defect (AVSD), total anomalous pulmonary venous return (TAPVR), left ventricular outflow tract obstruction (LVOTO), right ventricular outflow tract obstruction (RVOTO), atrial septal defect (ASD)/ventricular septal defect (VSD), and patent ductus arteriosus (PDA)]. Results:Nine articles were finally included, including two Chinese and seven English articles. Among them, 8 articles had CHD as the outcome, 5 articles had ASD/VSD as the outcome, 4 articles had CTD as the outcome, 3 articles had LVOTO as the outcome, 2 articles had PDA as the outcome, and 1 article had RVOTO as the outcome. An analysis was conducted on 8 articles with CHD as the outcome. After heterogeneity testing, I 2 = 88.5% and P < 0.001, indicating significant heterogeneity. A random effect model was used for meta-analysis, and the combined OR value (95% CI) was 1.51 (1.40 - 1.62). The results of CHD subgroup analysis showed that the combined OR values (95% CI) for ASD/VSD, CTD, LVOTO, PDA, and RVOTO were 1.68 (1.53 - 1.84), 1.64 (1.29 - 2.09), 2.89 (1.82 - 4.61), 1.78 (1.53 - 2.08), and 0.81 (0.64 - 1.03), respectively. Conclusion:Maternal arsenic exposure during pregnancy is associated with development of offspring CHD, including ASD/VSD, CTD, LVOTO, and PDA as the common lesions in offspring CHD.

Harnessing the Potentialities of Arsenic Resistant Fungal Endophytes for Improved Growth Promoting Traits under in vitro Condition

Endophytic fungi enhance the plant’s ability to tolerate stressful conditions including heavy metal stress via secretion of numerous secondary metabolites. However, the role of heavy metal resistant fungal endophytes in growth promotion of plants in extreme environments is need to be understood. Therefore, eight endophytic fungal isolates having arsenic tolerance potential up to 2000 ppm explored from the arsenic stressed plants were subjected to various in vitro growth promoting traits viz., phytohormones production, phosphate solubilization, siderophore production, ammonia production, HCN production and ACC deaminase activity under normal and arsenic stress (100 ppm) condition. Indole acetic acid produced by fungal endophytes ranged between 120-610 ?g/ mL, which was reduced to 50-340 ?g/ mL when they were grown on arsenic induced medium. In the siderophore production test, fungal isolate S3P1S1 produced significantly higher siderophore (96 ±?0.002 ?mol) compared to other isolates and reference culture. In addition, HCN production was observed in only one isolate. Therefore, present study clearly identified specific traits in the fungal endophytes, which make them good candidates as PGPR and might contribute to plant adaption to arsenic contaminated soils. These fungal endophytes, possessing metal tolerance as well growth promoting properties under in vitro conditions could have vital implications for the agricultural sector if used as biofertilizer.

Contenido de arsénico, conocimiento y actitud en el consumo del agua de pozo familiar / Arsenic content, knowledge and attitude in family well water consumption / Conteúdo de arsênico, conhecimento e atitude em relação ao consumo doméstico de água de poço

La contaminación por arsénico del agua de consumo humano, es un problema de salud pública, porque produce diversas enfermedades cancerígenas y de piel. Objetivo. Determinar niveles de arsénico en el agua de pozos, y evaluar el grado de conocimiento y actitud sobre el consumo del agua familiar. Materiales y métodos. Se utilizaron 96 muestras del agua de pozos del distrito de Juliaca. Las cuales se analizaron en laboratorio de Unidad de Servicios de Análisis Químicos de la Facultad de Química - Universidad Nacional Mayor de San Marcos-Lima, mediante la técnica Espectrofotometría de Absorción Atómica con Horno de Grafito. Los datos de arsénico fueron procesados estadísticamente mediante el diseño completamente al azar. Asimismo, la descripción del conocimiento y actitud del consumo de agua familiar se realizó aplicando la técnica de la encuesta y el instrumento fue un cuestionario de 11 ítems para la variable conocimiento y 7 para la variable actitud, con respuestas de alto, medio y bajo para conocimiento y buena, regular y mala calificadas con escala de Likert. Resultados. La concentración promedio fue 0.031 mg de As/L de agua y entre zonas hubo semejanza (p>0.05). En el grado de conocimiento sobre contaminación con arsénico en el agua de consumo humano respondieron el 40.81 % con calificación alta y el 59.19% están entre medio y bajo; en actitud, la calificación buena obtuvo menos del 50 % de encuestados y el resto están entre regular y mala. Conclusiones. El contenido arsenical en el agua de pozos supera los límites máximos permisibles según Organización Mundial de Salud y más del 50% se exponen al agua contaminada.

Arsenic contamination of drinking water is a public health problem, because it causes various carcinogenic and skin diseases. Objective. To determine arsenic levels in well water, and to evaluate the degree of knowledge and attitude about family water consumption. Materials and methods. Ninety-six samples of well water from the district of Juliaca were used. These were analyzed in the laboratory of the Chemical Analysis Services Unit of the Faculty of Chemistry - Universidad Nacional Mayor de San Marcos-Lima, using the technique Atomic Absorption Spectrophotometry with Graphite Furnace. The arsenic data were statistically processed using a completely randomized design. Likewise, the description of the knowledge and attitude of family water consumption was carried out by applying the survey technique and the instrument was a questionnaire of 11 items for the knowledge variable and 7 for the attitude variable, with answers of high, medium and low for knowledge and good, regular and bad rated with a Likert scale. Results. The average concentration was 0.031 mg As/L water and there was similarity between zones (p>0.05). In the degree of knowledge about arsenic contamination in drinking water, 40.81% responded with high qualification and 59.19% were between medium and low; in attitude, the good qualification obtained less than 50% of respondents and the rest were between regular and bad. Conclusions. The arsenic content in well water exceeds the maximum permissible limits according to the World Health Organization and more than 50% are exposed to contaminated water.

A contaminação da água potável por arsênico é um problema de saúde pública, pois causa várias doenças de pele e carcinogênicas. Objetivo. Determinar os níveis de arsênico na água de poço e avaliar o grau de conhecimento e atitude em relação ao consumo doméstico de água. Materiais e métodos. Foram utilizadas 96 amostras de água de poço do distrito de Juliaca. Elas foram analisadas no laboratório da Unidade de Serviços de Análises Químicas da Faculdade de Química da Universidade Nacional Mayor de San Marcos-Lima, usando a técnica de Espectrofotometria de Absorção Atômica com Forno de Grafite. Os dados sobre arsênico foram processados estatisticamente usando um desenho completamente aleatório. Da mesma forma, a descrição do conhecimento e da atitude do consumo familiar de água foi realizada aplicando a técnica de pesquisa e o instrumento foi um questionário de 11 itens para a variável conhecimento e 7 para a variável atitude, com respostas de alto, médio e baixo para o conhecimento e classificado como bom, regular e ruim em uma escala Likert. Resultados. A concentração média foi de 0,031 mg As/L de água e houve similaridade entre as zonas (p>0,05). Quanto ao grau de conhecimento sobre a contaminação por arsênico na água potável, 40,81% responderam com uma pontuação alta e 59,19% ficaram entre médio e baixo; quanto à atitude, a pontuação boa foi obtida por menos de 50% dos entrevistados e o restante ficou entre regular e ruim. Conclusões. O teor de arsênico na água de poço excede os limites máximos permitidos de acordo com a Organização Mundial da Saúde e mais de 50% estão expostos à água contaminada.

Metal Exposure in Arica, Chile: Examining Toxic Elements / Análisis de exposición a metales en Arica, Chile: niveles de elementos tóxicos

BACKGROUND: Bioaccumulation of toxic metals in the population is associated with adverse health effects. Although some elements are essential for humans, high levels of exposure can be dangerous. OBJECTIVE: To describe the levels of Inorganic Arsenic (AsIn), Cadmium (Cd), Chromium (Cr), and Mercury (Hg) in urine, and Lead (Pb) in blood in the population of Arica, Chile. METHODOLOGY: Descriptive study. Beneficiaries of the Health Surveillance Program of Law 20.590 in sites of higher risk of exposure in the commune of Arica were considered eligible. The results of biological samples to measure their concentrations of AsIn, Cd, Cr, Hg in urine, and Pb in blood between August 2016 and May 2021 are described. RESULTS: 9520 samples from a population with a mean age of 40.5 years were studied. 4.21% of the adult population and 6.57% of the children had AsIn values above 35 μg/L, while at least 95 % of the total samples had levels below 33 μg/L. At least 90 % of the samples had Cd levels below 1.1 μg/L, and 8.44 % had Cd levels above 2 μg/L, higher in males (11.67%). There were no values above the reference in children. 99.77% and 99.33% had Cr and Pb values below the reference limit, respectively (using the lowest reference range established by Chile Ministry of Health (MINSAL) < 5 μg/L). Children did not present risk values for Cr, and 0.16% presented Pb concentrations between 5-10 μg/dL. All samples presented Hg concentrations below risk levels (< 10 μg/L). CONCLUSIONS: The results of this study suggest that a small percentage of the samples analyzed in the beneficiary population of Arica register metal concentration levels above national reference levels established by MINSAL, mainly AsIn, Cd, and Pb. It is essential to continue biomonitoring to reduce and prevent exposure to these metals, which can have harmful effects on human health.

ANTECEDENTES: La bioacumulación de metales en la población está asociada a efectos adversos y pueden ser peligrosos. OBJETIVO: Describir los niveles de Arsénico Inorgánico (AsIn), Cadmio (Cd), Cromo (Cr), Mercurio (Hg) y Plomo (Pb) en la población de Arica, Chile. MATERIALES Y MÉTODOS: Estudio descriptivo. Se incluyeron todas las personas beneficiarias del Programa de Vigilancia de Salud de la Ley 20.590 en sitios de riesgo de mayor exposición en la comuna de Arica entre agosto 2016 y mayo 2021. RESULTADOS: Se estudiaron 9.520 muestras provenientes de una población con una edad media de 40.5 años. 4.21% de la población adulta y el 6.57% de los niños presentaron valores de AsIn superiores a 35 μg/L y al menos el 95% de las muestras totales tenía niveles inferiores a 33 μg/L. Más del 90 % de las muestras tuvieron niveles de Cd menores a 1.1 μg/L y un 8.44% registró niveles de Cd superiores 2 μg/L. El 99.77% y 99.33% exhibieron valores normales de Cr y Pb, respectivamente. Todas las muestras presentaron concentraciones de Hg por debajo de los niveles de riesgo (< 10 μg/L). CONCLUSIONES: Los resultados sugieren que un porcentaje pequeño de la población de Arica registra niveles de concentración de metales por sobre niveles de referencia nacional establecidos por el Ministerio de Salud de Chile, principalmente de AsIn, Cd y Pb. Es importante continuar con la vigilancia para reducir y prevenir la exposición a estos metales, que pueden generar efectos nocivos en la salud humana.

Arsenicals Review: Poison vis-a-vis Medicine

Arsenic tops the list of priority list of hazardous substances 2022. People are frequently exposed to the environmental pollutant metalloid arsenic through their food, water, air, and soil. Arsenic is famous for its toxic effects. However, arsenicals have recently gained attention due to promising clinical trials for the treatment of acute myeloid leukemia. Presently numerous studies on arsenic's anticancer effects have been done. So a review was conducted on the use of arsenicals as poison and medicine. Arsenical was used as a powerful medicine in the BC era. But arsenical became famous as "the King's Poison" and "the Poison of the King" due to its use as poison. But the development of Marsh’s Test in the 18th century led to a decrease in the use of arsenicals as poison. In the 18th century, arsenicals were used as medicine to treat a variety of diseases such as fever, rheumatism, psoriasis, and syphilis. The development of antibiotics, new, safer chemotherapeutic agents, and radiotherapy halted its use as medicine. The dose and form of arsenicals make them medicine or poison. Many literary works reveal that arsenic's journey as “medicine” and “poison” is still ongoing in the twenty-first century.

Arsenic Trioxide: Pharmacological Applications / Trióxido de Arsénico: Aplicaciones farmacológicas

Background: Arsenic trioxide is a chemical compound that has been used as a treatment for various diseases. Despite being potentially toxic, this compound has been used as a therapy to treat Acute Myeloid Leukemia and is being investigated as a possible treatment for different types of cancer. Objectives: The present review aims to describe the use and studies reported in the literature of Arsenic Trioxide as a possible therapeutic agent for Acute Myeloid Leukemia, Acute Promyelocytic Leukemia, Chronic Myeloid Leukemia, Multiple Myeloma, Myelodysplastic Syndrome, Hepatocellular Carcinoma, Lung Cancer, Neuroblastoma, Breast Cancer, Aplastic Hepatitis C, and HIV-1. Methods: A systematic review was conducted using databases (Elsevier, Google Scholar, PubMed) to compile documents published before December 2023. Results:Multiple pharmacological applications of arsenic trioxide have been reported to treat acute and chronic myeloid leukemia. Arsenic trioxide has been shown to inhibit angiogenesis, which helps treat multiple myeloma. Several studies have shown and suggested the effectiveness of arsenic trioxide as a treatment of hepatocellular carcinoma, lung cancer, neuroblastoma, prostate cancer, breast cancer, aplastic anemia, hepatitis C, and HIV-1. Conclusion: Despite potentially toxic effects, Arsenic compounds are therapeutic agents for multiple diseases, from syphilis to cancer. In recent years, more efficient ways have been investigated to deliver and find the specific dose to treat the disease, causing the fewest possible adverse effects.

Antecedentes: El trióxido de arsénico es un compuesto químico que se ha utilizado como tratamiento de diversas enfermedades. A pesar de ser potencialmente tóxico, este compuesto se ha utilizado como terapia para tratar la leucemia mieloide aguda y se está investigando como posible tratamiento para diferentes tipos de cáncer. Objetivos: La presente revisión pretende describir el uso del trióxido de arsénico como posible agente terapéutico para la leucemia mieloide aguda, la leucemia promielocítica aguda, la leucemia mieloide crónica, el mieloma múltiple, el síndrome mielodisplásico, el carcinoma hepatocelular, el cáncer de pulmón, el neuroblastoma, el cáncer de mama, la hepatitis C aplásica y el VIH-1. Métodos: Se realizó una revisión sistemática utilizando bases de datos (Elsevier, Google Scholar, PubMed) para recopilar documentos publicados antes de diciembre de 2023. Resultados: Se ha informado de múltiples aplicaciones farmacológicas del trióxido de arsénico para tratar la leucemia mieloide aguda y la leucemia mieloide crónica. Se ha demostrado que el trióxido de arsénico inhibe la angiogénesis, lo que resulta útil para el tratamiento del mieloma múltiple. Varios estudios han demostrado y sugerido la eficacia del trióxido de arsénico como tratamiento del carcinoma hepatocelular, el cáncer de pulmón, el neuroblastoma, el cáncer de próstata, el cáncer de mama, la anemia aplásica, la hepatitis C y el VIH-1. Conclusión: A pesar de tener un efecto potencialmente tóxico, los compuestos de arsénico destacan como agentes terapéuticos para múltiples enfermedades, desde la sífilis hasta el cáncer. En los últimos años, se han investigado formas más eficientes de administrar y encontrar la dosis específica para poder tratar la enfermedad, causando los menores efectos adversos posibles.

Antagonism of Lentinan on sodium arsenite induced hepatotoxicity in mice / 公共卫生与预防医学

Objective To explore the intervention effects of lentinan on sodium arsenite (SA) induced hepatotoxicity in mice. Methods Healthy male C57BL/6 mice were used as experimental subjects and divided into 4 groups, namely control group, SA treatment group, lentinan intervention + SA exposure group, and lentinan intervention control group. The mice were given oral SA (10.0 mg/kg.bw, once every other day) for 14 days, and then the liver tissues and serum samples were collected. Hematoxylin-eosin (HE) was used to evaluate the characteristics of hepatic pathological damage. Enzyme-linked immunosorbent assay (ELISA), Flow Cytometry (FC) and Western-blotting (WB) were used to detect the levels of hepatic function, oxidative stress, CD4+ type 17 helper T cells (Th17), and inflammatory cytokines. Results Compared with the control group, the arsenic exposure group showed obvious hepatic pathological injury and increased levels of serum ALT (8.78±0.76 vs 5.47±0.49) and AST (12.42±1.87 vs 7.14±0.57), FC experiments showed that the Th17 content in liver tissues increased (67.70±4.94 vs 7.36±1.50), and ELISA showed that the antioxidant GSH content decreased (593.40±23.25 vs 730.94±30.81), and the levels of MDA (74.56±7.63 vs 49.90±6.42) and proinflammatory cytokines IL-17A (162.48±10.75 vs 118.53±7.92) and IL-1β (512.50±24.78 vs 462.48±22.15) increased in hepatic tissues (P < 0.05). Compared with the arsenic exposure group, the lentinan showed a significant antagonistic effect after intervention (P < 0.05). Compared to SA exposure group, WB analysis showed that compared with the arsenic exposure group, the expression levels of IL-17A (0.47±0.08 vs 0.89±0.11) and NLRP3 inflammasome (0.80±0.09 vs 1.09±0.16) in the liver tissues of the lentinan intervention group were significantly decreased (P < 0.05). Conclusion Lentinan alleviates SA-induced hepatic injury in mice, which may be mediated through the inhibition of Th17-IL-17A inflammatory signaling.

Osteonecrosis of the jaw induced by arsenic trioxide therapy in acute promyelocytic leukemia patient: a case report and literature review / 口腔疾病防治

Objective @#To investigate the etiology, clinical manifestations, treatment and prevention of jaw necrosis caused by arsenic trioxide to provide a reference for clinical diagnosis and treatment. @*Methods@#To analyze the clinical data and related literature of patients with jaw necrosis caused by acute promyelocytic leukemia treated with arsenic trioxide@*Results@#We report a case of jaw necrosis caused by the use of arsenic trioxide (10 mg once a day for one month) during the treatment of acute promyelocytic leukemia. About 20 days after treatment, the patient developed right maxillary pain accompanied by gingival redness and swelling and mucosal ulcer, 14-17 teeth had buccal and palatal alveolar bone exposed, gingival mucosa was missing, gingival tissue was damaged to the bottom of vestibular groove, and palatal soft tissue was damaged to 5-8 mm of palatal suture. Due to the unstable condition of acute promyelocytic leukemia, the patient was given conservative treatment such as oral vitamin and Kangfuxin liquid gargle to keep his mouth clean. Drug induced jaw necrosis reported in the literature can be caused by bisphosphonates. Arsenic trioxide can also cause local jaw necrosis. Clinically, it is often manifested as long-term wound nonunion, pus, alveolar bone or jaw bone exposure, dead bone formation, accompanied by pain, loose teeth, facial swelling and other symptoms. Anti inflammation, debridement and surgical removal of dead bone are commonly used treatment methods.@*Conclusion @# In clinical practice, we should be alert to drug-induced jaw necrosis and strengthen prevention.

Effects of arsenic exposure on E2 and TRH and their receptor mRNA expressions in rats / 环境与职业医学

Background Arsenic can enter the hypothalamus to induce estrogen effect and interfere with the function of the neuroendocrine system. The thyroid endocrine system (hypothalamic-pituitary-thyroid axis) is one of the main endocrine systems, and the mechanism of arsenic-induced thyroid endocrine toxicity is still unclear. Objective To investigate the effects of different arsenic exposure levels on estradiol (E2), hypothalamic thyrotropin-releasing hormone (TRH), and their receptor (ERα, ERβ, and TRHR) mRNAs in rats and the possible hypothalamic toxic pathway and mechanism. Methods Seventy Wister rats were randomly divided a control group (sterile water); low-, medium-, and high-dose arsenic exposure groups [0.8, 4.0, and 20.0 mg·kg−1 sodium arsenite (NaAsO2)]; estrogen receptor inhibitor (ICI182780) intervention + low-, medium-, and high-dose arsenic exposure groups; with 10 animals in each group, half male and half female. Rats in the arsenic exposure groups were exposed to NaAsO2 by drinking water for 19 weeks, and rats in the intervention groups were injected with 0.5 mg·kg−1 ICI182780 via tail vein at week 9, 3 times a week. The levels of E2 and TRH in serum of rats were detected by ELISA. The expression levels of estrogen receptor α (ERα), estrogen receptor β (ERβ), and TRH receptor (TRHR) mRNAs in hypothalamus of rats were detected by real-time PCR (RT-PCR). Results (1) E2 and its receptor mRNA: Compared with the control group, the serum E2 level of female rats was increased in the low-dose and the medium-dose arsenic exposure groups (P<0.05), and the serum E2 level of male rats was increased in the low-dose, the medium-dose, and the high-dose arsenic exposure groups (P<0.05), and the change of female E2 was greater than that of male rats. Compared with the control group, the relative expression levels of ERα mRNA and ERβ mRNA in female rats were increased in the low-dose, the medium-dose, and the high-dose arsenic exposure groups (P<0.05), so were the relative expression levels of ERα mRNA in male rats (P<0.05). (2) TRH and its receptor mRNA: Compared with the control group, the serum TRH level of female rats was increased in the high-dose arsenic group (P<0.05), the relative expression level of TRHR mRNA was increased in the low-dose, the medium-dose, and the high-dose arsenic exposure groups (P<0.05). Results (1) and results (2) suggested that females were more likely than males to have abnormal changes in E2, TRH, and related receptor genes after arsenic exposure. (3) Compared with female rats in the medium-high dose arsenic exposure group, the expressions of TRH and TRHR induced by arsenic exposure were inhibited after the intervention of ICI182780 (P<0.05), suggesting that arsenic in the hypothalamus may have toxic effects on TRH and TRHR by inducing estrogen-like effects. Conclusion Arsenic exposure can induce estrogen-like effects in the hypothalamus, interfere with thyroid function, and show dose-dependent and sex differences. E2 and TRH and their receptors may be the toxic pathway of arsenic-related estrogen-like effect.

Arsenic Content in Cordyceps： A Review / 中国实验方剂学杂志

Cordyceps， a unique precious Chinese herbal medicine in China， has the effects of tonifying the kidney and lungs， stopping bleeding， and resolving phlegm. It has definite clinical effects on diabetes， respiratory diseases （such as chronic obstructive pulmonary disease）， chronic kidney diseases， slow arrhythmia， and hyperlipidemia. We searched China National Knowledge Infrastructure （CNKI）， Wanfang Data， VIP， SpringerLink （Biomedical Sciences）， Embase， Proquest （Life Sciences）， PubMed， Cochrane Library， and SinoMed for the research on the arsenic content in Cordyceps. According to statistical analysis， arsenic in Cordyceps mainly exists in the non-toxic or low-toxic form. The arsenic-containing compounds in Cordyceps may be an arsenic-sugar compound with anticancer effect. The inorganic arsenic content in Cordyceps is lower than the arsenic standard stipulated by the State Food and Drug Administration. It remains uncertain whether different measurement methods can affect the results. The total arsenic content varies in Cordyceps from different producing areas， and the general rule of total arsenic content in Cordyceps produced in different provinces， districts， and counties cannot be obtained from the results of the existing studies. The arsenic content in Cordyceps is mainly concentrated in the insect part， which is significantly different from that in stroma， and no arsenic is detected in the mycelia. The soil arsenic content in the growing areas is generally high， which may be a main reason for the high arsenic content in Cordyceps. As a valuable medicinal material for tonifying and nourishing， Cordyceps still plays an irreplaceable role in disease prevention， health care， chronic disease management， and rehabilitation.

Mechanism of Learning and Memory Impairment in Rats Exposed to Arsenic and/or Fluoride Based on Microbiome and Metabolome / 生物医学与环境科学（英文）

OBJECTIVE@#Arsenic (As) and fluoride (F) are two of the most common elements contaminating groundwater resources. A growing number of studies have found that As and F can cause neurotoxicity in infants and children, leading to cognitive, learning, and memory impairments. However, early biomarkers of learning and memory impairment induced by As and/or F remain unclear. In the present study, the mechanisms by which As and/or F cause learning memory impairment are explored at the multi-omics level (microbiome and metabolome).@*METHODS@#We stablished an SD rats model exposed to arsenic and/or fluoride from intrauterine to adult period.@*RESULTS@#Arsenic and/fluoride exposed groups showed reduced neurobehavioral performance and lesions in the hippocampal CA1 region. 16S rRNA gene sequencing revealed that As and/or F exposure significantly altered the composition and diversity of the gut microbiome，featuring the Lachnospiraceae_NK4A136_group, Ruminococcus_1, Prevotellaceae_NK3B31_group, [Eubacterium]_xylanophilum_group. Metabolome analysis showed that As and/or F-induced learning and memory impairment may be related to tryptophan, lipoic acid, glutamate, gamma-aminobutyric acidergic (GABAergic) synapse, and arachidonic acid (AA) metabolism. The gut microbiota, metabolites, and learning memory indicators were significantly correlated.@*CONCLUSION@#Learning memory impairment triggered by As and/or F exposure may be mediated by different gut microbes and their associated metabolites.